Disease, injury, surgery or other disorders can lead to localized tissue damage. When bioactive materials are administered orally or parenterally to treat a local disorder, they often must be given in large amounts so that an effective amount of the bioactive material reaches the treatment site. These large amounts of administered bioactive materials can produce harmful side effects in other areas of the body where treatment is not needed. Thus, one significant challenge in the medical and pharmaceutical industry has been to deliver an effective amount of a bioactive material locally at a treatment site without producing unwanted systemic side effects.
A prime example of a situation where local therapy is needed with bioactive materials that produce unwanted systemic side effects is in the prevention of complications following the placement of a cardiovascular prosthetic device such as a prosthetic vascular graft, patch, or stent used to repair a damaged vessel. With the implantation of stents in particular (tubular devices intended to hold vessels or other lumens open and clear), restenosis, a re-narrowing of the vessel can occur. To prevent this re-narrowing, numerous pharmacological agents have been tested. Unfortunately, none have yet demonstrated an unequivocal reduction in the incidence of restenosis. One reason for the failure of these pharmacological therapies may be due to ineffective administration routes or protocols adopted to avoid the serious side-effects that could result from systemic administration of the proper dosage.
To address this problem, various researchers have proposed devices and methods for site-specific delivery of bioactive materials. Some of the proposed methods have included the systemic administration of therapeutic agents that have a specific affinity for the injured or diseased tissue or systemic administration of inactive agents followed by local activation. When dealing with the treatment of a vessel in particular, proposed methods have included the direct deposition of bioactive materials into an arterial wall through an intravascular delivery system and the local placement of bioactive material coated stents. Wilensky et al., Methods and Devices for Local Drug Delivery in Coronary and Peripheral Arteries, Trend Cardiovasc Med, vol. 3 (1993).
Other attempts to locally deliver bioactive materials to lumens have included angioplasty catheter dilation balloons with coatings of bioactive materials on the external surface of the balloon (e.g., U.S. Pat. Nos. 5,102,402 and 5,199,951). Other balloon catheters contain perforations in the wall of the balloon for infusion of bioactive materials such as the Wolinsky catheter or the “balloon within a balloon design” seen in U.S. Pat. No. 5,049,132. There are also systems that include proximal and distal balloons that are simultaneously inflated to isolate a treatment space within an arterial lumen. In this example, a catheter extends between the two balloons and includes a port that can deliver bioactive materials to the space between the inflated balloons. These approaches, however, often disrupt fluid flow through the lumen and reduce distal tissue perfusion during bioactive material delivery. Other catheters such as the Stack perfusion catheter and the catheter embodied in U.S. Pat. No. 5,181,911 were designed to facilitate drug delivery without disrupting distal tissue perfusion. These devices, however, are bulky and limited in their clinical applications.
The efficacy of the described devices and methods turns on a number of factors including the local conditions and vasculature of the treatment site. For instance, one efficacy factor includes the amount of time that a delivered bioactive material will stay resident locally before being carried downstream by circulating fluids, including in one example, circulating blood. To the extent these systems allow the bioactive materials to be carried away from the treatment site, they run the risk of applying the bioactive material to areas of the body where such agents may not be beneficial and leaving the intended area untreated. Further, and as stated, a number of the described devices and methods block the flow of fluids through the lumen during bioactive material delivery. This blockage can reduce the effectiveness of the described devices and methods by leading to unwanted side effects related to the blockage of fluid flow through the lumen.
Based on these issues, there exists a need in the art for systems and methods that can deliver and sustain appropriate concentrations of bioactive materials at a treatment site within a lumen without blocking fluid flow through the lumen during bioactive material delivery. The present invention provides such systems and methods.